Carolin Victoria Schneider

RWTH Aachen University

Background & Aims Homozygosity for the Pi*Z variant of the gene that encodes the alpha-1 antitrypsin peptide (AAT), called the Pi*ZZ genotype, causes a liver and lung disease called alpha-1 antitrypsin deficiency. Heterozygosity (the Pi*MZ genotype) is a risk factor for cirrhosis in individuals with liver disease. Up to 4% of Caucasians have the Pi...

Nonalcoholic fatty liver disease (NAFLD) is a prevalent, heritable trait that can progress to cancer and liver failure. Using our recently developed proxy definition for NAFLD based on chronic liver enzyme elevation without other causes of liver disease or alcohol misuse, we performed a multi-ancestry genome-wide association study in the Million Ve...

Importance Telomeres protect DNA from damage. Because they shorten with each mitotic cycle, leukocyte telomere length (LTL) serves as a mitotic clock. Reduced LTL has been associated with multiple human disorders. Objective To determine the association between LTL and overall as well as disease-specific mortality and morbidity. Design, Setting, a...

Nonalcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver disease. Using a proxy NAFLD definition of chronic elevation of alanine aminotransferase (cALT) levels without other liver diseases, we performed a multiancestry genome-wide association study (GWAS) in the Million Veteran Program (MVP) including 90,408 cALT cases and 128,1...

Introduction: Vitamin E supplementation is recommended for the treatment of non-alcoholic fatty liver disease (NAFLD) for nondiabetic patients, but its preventative effects are unclear. Methods: We assessed dietary Vitamin E intake with disease phenotypes and evaluated Vitamin E levels with the development of NAFLD. Results: Data from >210,000...

Acute-on-chronic liver failure (ACLF) defines a heterogeneous syndrome involving acute decompensation in patients with pre-existing liver disease accompanied by (multi-)organ failure. This study aimed to develop a simple, reliable machine learning (ML) model to predict mortality in ACLF patients receiving intensive care unit (ICU) treatment. Data f...

Vision-language models (VLMs) can analyze multimodal medical data. However, a significant weakness of VLMs, as we have recently described, is their susceptibility to prompt injection attacks. Here, the model receives conflicting instructions, leading to potentially harmful outputs. In this study, we hypothesized that handwritten labels and watermar...

Background Metabolic dysfunction‐associated steatotic liver disease (MASLD) affects up to 30% of Western populations. While obesity is a recognized risk factor, MASLD does not develop in all obese individuals, highlighting the need to understand genetic and environmental interactions. The PNPLA3 I148M variant has been identified as a key genetic ri...

Background and aims: Hepatocellular carcinoma (HCC) is a highly fatal tumor, for which early detection and risk stratification is crucial, yet remains challenging. We aimed to develop an interpretable machine-learning framework for HCC risk stratification based on routinely collected clinical data. Methods: We leverage data obtained from over 900,0...

The aggressiveness of prostate cancer, the most common cancer in men worldwide, is primarily assessed based on histopathological data using the Gleason scoring system. While artificial intelligence (AI) has shown promise in accurately predicting Gleason scores, these predictions often lack inherent explainability, potentially leading to distrust in...

Background & Aim An unbiased genome-first approach can expand the molecular understanding of specific genes in disease-agnostic biobanks for deeper phenotyping. TM6SF2 represents a good candidate for this approach due to its known association with steatotic liver disease (SLD). Methods We screened participants with whole-exome sequences in the Pen...

Artificial intelligence (AI) systems have substantially improved dermatologists' diagnostic accuracy for melanoma, with explainable AI (XAI) systems further enhancing clinicians' confidence and trust in AI-driven decisions. Despite these advancements, there remains a critical need for objective evaluation of how dermatologists engage with both AI a...

Aim To examine the association between the use of incretin-based drugs [glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl peptidase-4 inhibitors (DPP-4Is)] and the risk of cholangiocarcinoma (CCA) in the United States. Methods This large population-based, retrospective cohort study using the TriNetX datasets included adult patients...

Background Metabolic dysfunction‐associated steatotic liver disease (MASLD) affects approximately 20%–30% of the general population and is linked to high‐caloric western style diet. However, there are little data that specific nutrients might help to prevent steatosis. Methods We analysed the UK Biobank (ID 71300) 24 h‐nutritional assessments and...

Vision-language artificial intelligence models (VLMs) possess medical knowledge and can be employed in healthcare in numerous ways, including as image interpreters, virtual scribes, and general decision support systems. However, here, we demonstrate that current VLMs applied to medical tasks exhibit a fundamental security flaw: they can be attacked...

Background and Aims Alpha‐1 antitrypsin deficiency is an inherited disorder caused by alpha‐1 antitrypsin (AAT) mutations. We analysed the association between alcohol intake and liver‐related parameters in individuals with the heterozygous/homozygous Pi*Z AAT variant (Pi*MZ/Pi*ZZ genotype) found in the United Kingdom Biobank and the European Alpha1...

Background Common variants of the max-like protein X (MLX)-interacting protein-like ( MLXIPL ) gene, encoding the transcription factor carbohydrate-responsive element-binding protein, have been shown to be associated with plasma triglyceride levels. However, the role of these variants in steatotic liver disease (SLD) is unclear. Methods We used a...

Background and Aims Primary biliary cholangitis (PBC) is a chronic, immune‐mediated liver disease that can lead to fibrosis and cirrhosis. In this cohort study, we aimed to investigate morbidity and mortality in conjunction with metabolomic changes of PBC in a UK population‐based cohort. Methods 454 participants with PBC and 908 propensity score (...

LINKED CONTENT This article is linked to Schneider et al papers. To view these articles, visit https://doi.org/10.1111/apt.17958 and https://doi.org/10.1111/apt.17986

Background The prevalence of at‐risk metabolic dysfunction‐associated steatohepatitis (at‐risk MASH) has not been systematically assessed. Aim To delineate the prevalence of at‐risk MASH in a large population‐based cohort. Methods We conducted a cross‐sectional analysis of 40,189 patients in the UK Biobank who underwent liver MRI. Hepatic steatos...

Background & Aims Changes in gut microbiota in metabolic dysfunction-associated steatotic liver disease (MASLD) are important drivers of disease progression towards fibrosis. Therefore, reversing microbial alterations could ameliorate MASLD progression. Oat beta-glucan, a non-digestible polysaccharide, has shown promising therapeutic effects on hyp...

The objective of this study is to define CT imaging derived phenotypes for patients with hepatic steatosis, a common metabolic liver condition, and determine its association with patient data from a medical biobank. There is a need to further characterize hepatic steatosis in lean patients, as its epidemiology may differ from that in overweight pat...

Aims/hypothesis We aimed to determine whether the use of glucagon-like peptide-1 receptor agonists (GLP-1RA) in individuals with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus decreases the risk of new-onset adverse cardiovascular events (CVEs) and mortality rate compared with other glucose-lowering drugs in a real setting a...

Importance Racial disparities in liver transplant (LT) for hepatocellular carcinoma (HCC) may be associated with unequal access to life-saving treatment. Objective To quantify racial disparities in LT for HCC and mortality after LT, adjusting for demographic, clinical, and socioeconomic factors. Design, Setting, and Participants This cohort study...

https://www.aasld.org/the-liver-meeting/deep-phenotyping-tm6sf2-characterize-hepatic-steatosis-plasma-lipid-traits-and

Background & Aims Non-alcoholic fatty liver disease (NAFLD) is characterised by the accumulation of lipid droplets (LDs) within hepatocytes. Perilipin 2 (PLIN2) is the most abundant protein in hepatic LDs and its expression correlates with intracellular lipid accumulation. A recently discovered PLIN2 coding variant, Ser251Pro (rs35568725), was foun...

Background The hepatoprotective effects of aspirin have been observed in individuals with viral hepatitis; however, its impact on the general population remains uncertain. Understanding the association between aspirin use and the development of liver diseases is crucial for optimizing preventive strategies. Methods We identified individuals with a...

Background and aims: Genetic risk factors are major determinants of chronic liver disease (CDL) progression. Patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M polymorphism and alpha-1 antitrypsin E342K variant, termed PiZ, are major modifiers of metabolic CLD. Both variants are known to affect metabolic CLD via increased endopl...

Background: Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver-related morbidity in people with and without diabetes, but it is underdiagnosed, posing challenges for research and clinical management. Here, we determine if natural language processing (NLP) of data in the electronic health record (EHR) could identify undiagnosed pati...

Background Non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease are among the most common liver diseases worldwide, and there are currently no Food and Drug Administration (FDA)-approved treatments. Recent studies have focused on lifestyle changes to prevent and treat NAFLD. Omega-3 supplementation is associated with improved outco...

LINKED CONTENT This article is linked to Schneider et al papers. To view these articles, visit https://doi.org/10.1111/apt.17566 and https://doi.org/10.1111/apt.17611

Background: Helicobacter pylori colonizes the human stomach. Infection causes chronic gastritis and increases the risk for gastroduodenal ulcer and gastric cancer. Its chronic colonization in the stomach triggers aberrant epithelial and inflammatory signals, that are also associated with systemic alterations. Methods: Using PheWAS analysis in mo...

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by chronic inflammation and progressive fibrosis of the biliary tree. The majority of PSC patients suffer from concomitant inflammatory bowel disease (IBD), which has been suggested to promote disease development and progression. However, the molecular mechani...

Background Metabolic (dysfunction-)associated fatty liver disease (MAFLD) is a common liver disease, formerly known as nonalcoholic fatty liver disease (NAFLD). The discussion of renaming NAFLD to MAFLD reflects the complex pathophysiology and heterogeneous clinical course of this disease.Objectives In this review, the factors contributing to the d...

Importance: Given the burden of chronic liver disease on the health care system, more information on the hepatoprotective association of statins in the general population is needed. Objective: To examine whether regular statin use is associated with a reduction in liver disease, particularly hepatocellular carcinoma (HCC) and liver-related death...

Background and Aims Genetic inactivation and pharmacologic inhibition of the microsomal triglyceride transfer protein (MTP; gene name MTTP) inhibits hepatic secretion of VLDL, thereby reducing serum lipids and apoB at the expense of increasing hepatic steatosis. Little is known about the effects of missense variants in MTTP on hepatic and circulati...

Background: Irritable bowel syndrome (IBS) is one of the most common functional digestive disorders. Our understanding about its comorbidities, biomarkers, or long-term risks is still incomplete. Objective: To characterize comorbidities and biomarkers for IBS and establish the effect of IBS on overall- and cause specific mortality. Methods: We...

Mental health profoundly impacts inflammatory responses in the body. This is particularly apparent in inflammatory bowel disease (IBD), in which psychological stress is associated with exacerbated disease flares. Here, we discover a critical role for the enteric nervous system (ENS) in mediating the aggravating effect of chronic stress on intestina...

Obesity is a growing worldwide epidemic that carries numerous metabolic complications including increased risk of type 2 diabetes (T2D), cardiovascular disease (CVD), and non-alcoholic fatty liver disease (NAFLD). Multiple genome-wide association studies (GWAS) have associated the PPP1R3B locus with cardiometabolic traits including fasting glucose...

Background & aims: Budd-Chiari syndrome (BCS) is a rare and potentially life-threatening disorder characterized by obstruction of the hepatic outflow tract. It is unknown whether patients with BCS represent a high risk for severe disease and mortality from coronavirus disease 2019 (COVID-19). Thus, we aimed to assess hospitalization rates, severe d...

Nonalcoholic fatty liver disease is common and highly heritable. Genetic studies of hepatic fat have not sufficiently addressed non-European and rare variants. In a medical biobank, we quantitate hepatic fat from clinical computed tomography (CT) scans via deep learning in 10,283 participants with whole-exome sequences available. We conduct exome-w...

To evaluate clinical characteristics and factors associated with survival among liver transplantation (LT) recipients with Budd-Chiari syndrome (BCS), with or without transjugular intrahepatic portosystemic shunt (TIPS), in the post-Model for End-stage Liver Disease era. Methods: We extracted data from the United Network for Organ Sharing databas...

Coeliac disease (CeD) is characterized by gliadin-induced intestinal inflammation appearing in genetically susceptible individuals, such as HLA-DQ2.5 carriers. CeD, as well as other chronic intestinal disorders, such as Crohn's disease (CD) and ulcerative colitis, has been associated with increased morbidity and mortality, but the causes are unknow...

Background: Lichen planus (LP) is a relative frequent mucocutaneous inflammatory disease affecting the skin, skin appendages, and mucosae, including oral mucosae, and less frequently anogenital area, conjunctivae, esophagus, or larynx. Objective: To estimate the association of LP, with emphasis on dermatological and gastrointestinal conditions,...